Microfluidic technology refers to a reaction system which could handle a small amount of liquid or samples (10−9-10−18 L) in microchannels in the scale of tens to hundreds of microns (Whitesides, Nature (2006) 442:368-73). The first application of microfluidic technology in biochemical analysis is the research of capillary electrophoresis. Because of its rapid and high-throughput analysis capability on small sample volumes and its high sensitivity and integration, microfluidic technology has been introduced to research and analysis at the levels of molecules (e.g., nucleic acid, protein, etc.), cells, tissues and organisms.
Cell positioning in a research system is usually the basis for the mechanism study of cell physiology. For example, cells are usually restricted in a fixed position for stable experimental conditions and continuous observations, in the studies of cell metabolism, cell growth and development and cell-environment interactions, etc. In the meanwhile, the distribution of cells in some special studies is also important. For example, the signal transmission between neurons can be very different due to the different arrangement of cells. In addition, motility screening of specific cells, cell culture and dynamic monitoring of cell conditions are also indispensable for mechanism studies of cells. Currently, microfluidic technology has been widely used in cell positioning, cell sorting, culture medium displacement and cell detection. However, a microdevice integrating all aforementioned steps is yet to be developed. The demand for such devices is even more urgent in the field of in vitro fertilization (IVF). IVF is a process by which egg cells are fertilized by sperm outside the body. The technology has become important treatment for human infertility. The major steps of conventional IVF include gamete collection, sperm motility screening, oocytes fertilization, medium replacement and early embryo culture. Since all the steps are conducted in Petri dish or tubes except oocyte collection, it's difficult to maintain a hemostasis with stable temperature and humidity. Besides, the conventional method is labor-intensive and poorly integrated. Therefore, a microdevice integrating cell positioning, cell motility screening, cell interaction, medium replacement and cell dynamic monitoring would be beneficial for improved IVF and assisted reproductive technology.
A microfluidic device was disclosed for embryo handling in U.S. Pat. No. 6,193,647. A constriction structure is included in their microdevice and an embryo can be parked at a desired location with the design. However, this device failed to select a single embryo out of a group, and it's not convenient for positioning and retrieval when dealing with more than one embryo. Moreover, shear force can hardly be avoided due to the constriction structure. John R. Dodgson et al. disclosed an apparatus for manipulation of cell, embryo or oocyte (Chinese Patent Application No. 200480033049.1). A well array is set in the microchannel and a fluidic passage is introduced to each well. This apparatus is suitable for handling of a group of more than two cells with multiple wells. However, the communication between the cells in adjacent wells is highly limited without gaps between the wells and it's difficult to build up of beneficial auto/paracrine factors from cell-cell contact or cell-environment crosstalk.